This program project is a continuation of multidisciplinary studies of the role of human papillomaviruses in the etiology of anogenital cancers. The individual projects address the epidemiology of these diseases, the host response in terms of pathogenesis and mechanisms of immunity and the biology of cells expressing papillomavirus genes. Four projects are proposed: The first project (0001) addresses the questions of immune response to papillomavirus infection and the role of immune modulation in progression to cancer. The second project (0002) examines the characteristics of cells proliferating in response to papillomavirus gene expression and will determine the mechanisms through which cofactors contribute to progression to malignancy. The third project (0004) continues case-control studies investigating the role of HPV in the development of anogenital cancers. The fourth project (0006) deals with an evaluation of prognosis of cases previously identified as HPV positive by cytology and molecular hybridization. The projects are supported by four cores which will provide molecular biological, histological and cytological support as well as biostatistical analysis and administrative oversight.